Determination of pancreatic ductal carcinoma histogenesis by analysis of mucous quality and K-ras mutation.
BACKGROUND
The authors sought to elucidate the histogenesis of pancreatic ductal carcinoma by correlating K-ras mutation with mucus type in normal epithelium, mucous cell hyperplasia (MCH), and carcinoma.


METHODS
Seventy-four solid-type carcinomas (SCs), 23 ductectatic-type carcinomas (DCs), and specimens of 24 normal pancreata were studied. By histochemical staining, normal duct epithelia, areas of MCH, and carcinomas were classified as having sulfo-type or sialo-type mucus. Foci from normal, DC, SC, sulfo-type, or sialo-type specimens were assessed for K-ras mutation at codon 12 by nested polymerase chain reaction and restriction fragment length polymorphism.


RESULTS
Of the SCs, 9 were sulfo-type and 65 were sialo-type; all DC specimens were sialo-type, and all normal epithelia were sulfo-type. All foci of sulfo-type, nonneoplastic epithelia were negative for K-ras mutation. In contrast, 124 of 313 sialo-type MCH foci (40%) had a K-ras mutation. Of 74 SCs, only 3 of 9 sulfo-type tumors (33%) were positive for the mutation. Sixty of 65 sialo-type SCs (92%) had a K-ras mutation, whereas 15 of 23 sialo-type DCs (65%) had a mutation. K-ras mutant carcinomas (including both SCs and DCs) were associated with K-ras mutant MCH in 109 of 198 MCHs (55%), whereas carcinomas without a K-ras mutation had mutations in 6 of 68 MCHs (9%). MCH in normal pancreata revealed K-ras mutations in 9 of 51 foci (18%). In addition, in K-ras mutant carcinomas, frequency of K-ras mutation in MCH increased from 27% (11 of 41 foci) of nonpapillary MCHs to 62% (98 of 157 foci) of papillary MCHs; but in K-ras wild-type carcinoma, the mutation rate in MCH was unchanged from 12% (3 of 26 foci) to 7% (3 of 42 foci) in nonpapillary and papillary foci, respectively.


CONCLUSIONS
These results suggest a strong relationship between the risk of pancreatic carcinoma and the presence of combinations of K-ras gene mutation, papillary growth, and expression of sialomucin in foci of MCH.
Matsubayashi
H
H
First Department of Pathology, Niigata University School of Medicine, Japan.
Watanabe
H
H
Nishikura
K
K
Ajioka
Y
Y
Kijima
H
H
Saito
T
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009077:Mucins / Q000378:metabolism; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D010183:Pancreatic Ducts / Q000378:metabolism / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism
D004273:DNA, Neoplasm; D009077:Mucins; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)